Inhibition of VEGF Signaling Reduces Diabetes-Exacerbated Brain Swelling, but Not Infarct Size, in Large Cerebral Infarction in Mice

Translational Stroke Research
Eunhee KimSunghee Cho

Abstract

In light of repeated translational failures with preclinical neuroprotection-based strategies, this preclinical study reevaluates brain swelling as an important pathological event in diabetic stroke and investigates underlying mechanism of the comorbidity-enhanced brain edema formation. Type 2 (mild), type 1 (moderate), and mixed type 1/2 (severe) diabetic mice were subjected to transient focal ischemia. Infarct volume, brain swelling, and IgG extravasation were assessed at 3 days post-stroke. Expression of vascular endothelial growth factor (VEGF)-A, endothelial-specific molecule-1 (Esm1), and the VEGF receptor 2 (VEGFR2) was determined in the ischemic brain. Additionally, SU5416, a VEGFR2 inhibitor, was treated in the type 1/2 diabetic mice, and stroke outcomes were determined. All diabetic groups displayed bigger infarct volume and brain swelling compared to nondiabetic mice, and the increased swelling was disproportionately larger relative to infarct enlargement. Diabetic conditions significantly increased VEGF-A, Esm1, and VEGFR2 expressions in the ischemic brain compared to nondiabetic mice. Notably, in diabetic mice, VEGFR2 mRNA levels were positively correlated with brain swelling, but not with infarct volume. Treatment...Continue Reading

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Citations

Apr 26, 2019·Journal of the American Heart Association·Natsue KishidaRyosuke Takahashi
Mar 22, 2020·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Blanca Fabiola Fajardo-FregosoMónica E Ureña-Guerrero
Apr 16, 2020·Cell Communication and Signaling : CCS·Yunxiang ZhouJianmin Zhang
Aug 11, 2020·Stroke; a Journal of Cerebral Circulation·Su Jing ChanVictor Nurcombe
Dec 15, 2018·Journal of Neuroscience Research·Robert P Ostrowski, John H Zhang
May 17, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Eunhee KimSunghee Cho
Mar 22, 2020·Translational Stroke Research·Poornima VenkatJieli Chen
Jun 27, 2020·Translational Stroke Research·Todd C PetersonMarion S Buckwalter
Jul 24, 2020·Neuroscience Letters·Kevin N Sheth, W Taylor Kimberly
Feb 23, 2021·Frontiers in Aging Neuroscience·Yi YaoJianzhao Luo
Jun 26, 2021·Pharmacology & Therapeutics·Sorabh Sharma, Craig E Brown

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Methods Mentioned

BETA
PCR
enzyme-linked immunosorbent assay

Software Mentioned

Image J
Axiovision
7500 Fast Real - Time PCR System

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